Sandra Horning, MD
Combining obinutuzumab (Gazyva) with chemotherapy in the first-line setting significantly reduced the risk of disease progression versus rituximab (Rituxan) plus chemotherapy in patients with follicular lymphoma, according to findings from the phase III GALLIUM study.
The safety profile was consistent with previously reported data for chemotherapy combinations with the two therapies, according to Genentech, which manufactures both anti-CD20 agents. Genentech intends to present the GALLIUM data at an upcoming medical meeting and enter discussions with regulatory authorities about a new indication for obinutuzumab.
"People with follicular lymphoma continue to need better initial treatment options because their disease is incurable and becomes more difficult to treat with each relapse," Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a statement.
The international phase III GALLIUM study included 1401 treatment-naive patients with indolent non-Hodgkin lymphoma, of whom 1202 patients had follicular lymphoma. Patients were randomized to obinutuzumab plus chemotherapy, followed by obinutuzumab alone (up to 2 years), or rituximab plus chemotherapy, followed by rituximab alone (up to 2 years). The chemotherapy regimens used were CHOP, CVP, or bendamustine, based on the discretion of the physicians at each study location.
The primary endpoint of the study was progression-free survival. Secondary outcome measures included response rate, overall survival, disease-free survival, and safety.
"GALLIUM is the second study in which Gazyva showed superior progression-free survival compared to Rituxan, when each was combined with chemotherapy,” said Horning.
The CLL11 trial was the first study to directly compare the agents. In the study, obinutuzumab plus chlorambucil reduced the risk of disease progression by 58% compared with rituximab plus chlorambucil in previously untreated patients with chronic lymphocytic leukemia (CLL; HR, 0.42; 95% CI, 0.33-0.54; P
<.0001). Among patients in the obinutuzumab arm, the most common adverse events were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea and diarrhea.
Based on data from the CLL11 trial the FDA approved obinutuzumab plus chlorambucil in November 2013 as a first-line treatment for patients with CLL.
In follicular lymphoma, the FDA approved obinutuzumab plus bendamustine followed by obinutuzumab alone for the treatment of patients who relapse after, or are refractory to, a rituximab-containing regimen.
The approval was based on the phase III GADOLIN study, in which obinutuzumab plus bendamustine followed by obinutuzumab monotherapy reduced the risk of disease progression by 52% compared with bendamustine alone (HR, 0.48; 95% CI 0.34-0.68; P <.0001) in patients with follicular lymphoma who progressed on rituximab-based therapy.
The best overall response (BOR) rate for the obinutuzumab cohort was 78.7%, including complete (CR) and partial response (PR) rates of 15.5% and 63.2%, respectively. The BOR was 74.7% for the control arm, with a CR rate of 18.7% and a PR rate of 56%. The median duration of response was not reached for the obinutuzumab arm versus 11.6 months with bendamustine alone.
The most frequently reported adverse events (AEs) in the obinutuzumab arm were infusion reactions (69%), low white blood cell counts (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), low platelet counts (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), low red blood cell counts (12%), general weakness (11%), and urinary tract infection (10%).
Low white blood cell counts (33%), infusion reactions (11%), and low platelet counts (10%), were the most common grade 3/4 AEs observed in patients receiving obinutuzumab. The most common serious AEs (>2%) included febrile neutropenia, neutropenia, infusion related reactions, sepsis, pneumonia, and pyrexia.
Obinutuzumab is a glycoengineered antibody against CD20. Through the glycoengineering process, sugar molecules are removed from immune-effector antibody cells in the posttranslational setting, significantly impacting antigen binding and function. Specifically, obinutuzumab is designed to lack fucose molecules.